RESEARCH STRATEGY A. Significance Advances in the understanding of the HIV-1 virus have led to the development of a large armamentarium of antiretroviral agents and the availability of a variety of efficacious strategies to prevent HIV transmission. However, large gaps exist between the potential for individual and population-level benefit inherent in these efficacious strategies, and the effectiveness observed clinically and at the population level. WHO estimates that expanded use of existing prevention tools could avert half of the 62 million new HIV infections projected to occur by 2015.[29] Similar gaps have been found with respect to the treatment of HCV among drug users, where clinical trials have demonstrated the superior efficacy of combination therapy for HCV with interferon, ribavirin and new direct acting antivirals, yet many HCV infected persons, particularly SUs, do not become engaged in HCV treatment Further, the impact of efficacious strategies is unevenly distributed, and significant health care disparities exist, particularly impacting racial and ethnic minorities and those without health insurance. As treatment has improved and HIV infected persons live longer, multiple comorbidities contribute to morbidity and mortality.[30] In areas where ART is widely available, liver disease, including HIV-HCV confection, has emerged as a significant cause of morbidity and mortality.[31-34] In some areas where ART has been implemented, drug resistant HIV has become more prevalent due to the complex interplay of individual barriers and access to care.[35,36] The Infectious Disease Core was established in CDUHR-III based on the recognition of the growing importance of biomedical issues affecting the HIV epidemic among drug users, including: the increasing role of sexual HIV transmission among SUs and high risk heterosexuals,[12,13,37] the hyperendemicity of hepatitis C virus (HCV) infection and HIV/HCV co-infection in drug users, issues with access to HCV. care, and HIV/TB confection. [38-42] During the course of CDUHR-III, biomedical advances, particularly antiretroviral therapy (ART), have further improved longevity and quality of life for PLWHA, but have not achieved their full potential because of barriers to full implementation.[43-45] Further, there was the recognition that the complexity and multilevel issues posed by the HIV epidemic among SUs and others would require both multidisciplinary study and multilevel intervention. The ID Core was created to enhance and support the biomedical knowledge base among CDUHR investigators in relevant scientific areas related to ID pathogenesis, natural history, and clinical care, and to foster the multidisciplinary study of HIV and other relevant issues among SUs. As newer biomedical interventions have been introduced (including PrEP, PEP, circumcision), there has been an increasing need for incorporating socio-behavioral expertise in successfully implementing these approaches. Further, the Affordable Health Care Act of 2010 may have a significant impact on the implementation phase of research translation. Thus, it is essential that CDUHR investigators are knowledgeable about biomedical trends and advances related to HIV and substance use and about changes in health care delivery. We will discuss several specific Issues relevant to HIV and infectious diseases affecting SUs that the IDB Core will address in the renewal. These issues are relevant to existing and planned projects within CDUHR and to the work of the IDB Core members. The specific topics are: A.1. Developments in HIV and substance use prevention and treatment; clinical implementation issues A.2. Health Care disparities A.S. HCV care for SUs, including for HIV-HCV co-infection A.4. Aging and comorbidities among PLWHA A.5. Health services for HIV and related conditions in SUs, and impact of changes in health care policy A.6. Genomic and Personalized Medicine for HIV, HCV, and related conditions of SUs A.7. The importance of Interprofessional Education (IPE)